A Phase 1/2 Study of MK-2870 plus EV plus Pembrolizumab in la/mUC

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

24 Sep 2024 → ongoing

Decision date (initial)

2024-09-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC · ​Pfizer/Astellas​

External identifiers

EU CT number

2023-506387-14-00

WHO UTN

U1111-1293-7631

ClinicalTrials.gov

NCT06483334

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Pharmacokinetic, Dose response, Pharmacodynamic, Safety, Pharmacogenomic, Pharmacogenetic

1. Part 1: To evaluate the safety and tolerability of MK-2870 in combination with EV
2. Not applicable: Part 2: To evaluate the safety and tolerability of MK-2870 in combination with pembrolizumab and EV
3. Not applicable: Part 2: To evaluate ORR, per RECIST 1.1 based on investigator assessment, of MK-2870 in combination with pembrolizumab and EV

Secondary objectives 6

1. Part 1: To evaluate ORR, per RECIST 1.1 based on investigator assessment, of MK-2870 in combination with EV
2. Not applicable: Part 2: To evaluate the DOR of MK-2870 in combination with pembrolizumab and EV per RECIST 1.1 based on investigator assessment.
3. Part 1: To characterize the PK profile of MK-2870 and EV when administered in combination
4. Part 1: To assess the immunogenicity of MK-2870 and EV when administered in combination
5. Not applicable: Part 2: To characterize the PK profile of MK-2870, EV, and pembrolizumab when administered in combination
6. Not applicable: Part 2: To assess the immunogenicity of MK-2870, EV, and pembrolizumab when administered in combination

Conditions and MedDRA coding

Advanced Urothelial Carcinoma

Regulatory references

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Must have histologically documented, locally advanced/metastatic urothelial carcinoma (la/mUC).
2. Must provide an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion demonstrating UC, not previously irradiated, and adequate for biomarker evaluation. A newly obtained biopsy is strongly preferred, but not required if archival tissue is evaluable.
3. Any AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Endocrine-related AEs adequately treated with hormone replacement are eligible.
4. PART 1 ONLY: Participants must have received platinum-based chemotherapy for treatment of la/mUC.
5. PART 1 ONLY: Participants must not have received >2 lines of therapy for la/mUC. Platinum-based chemotherapy followed by avelumab maintenance is considered 2 lines of therapy.
6. Not applicable: PART 2 ONLY: Participants must not have received prior systemic therapy for la/mUC.

Exclusion criteria 18

1. Known additional malignancy that is progressing or has required active treatment within the past 3 years.
2. Known active central nervous system metastases and/or carcinomatous meningitis.
3. Has Grade ≥2 peripheral neuropathy.
4. Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing.
5. Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (eg, Crohn’s disease, ulcerative colitis, or chronic diarrhea).
6. Has uncontrolled, significant cardiovascular disease or cerebrovascular disease and/or serious cardiovascular and cerebrovascular diseases within the 6 months preceding study intervention.
7. Has active keratitis or corneal ulcerations. Superficial punctate keratitis is allowed if the disorder is being adequately treated in the opinion of the investigator.
8. Has a history of uncontrolled diabetes.
9. Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
10. Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.
11. Not applicable: PART 2 ONLY: Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of study intervention. Inhaled or topical steroids are permitted in the absence of active autoimmune disease. Physiologic replacement doses of corticosteroids are permitted for participants with adrenal insufficiency.
12. Not applicable: PART 2 ONLY: Has an active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy.
13. Is human immunodeficiency virus (HIV)-infected and has a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease.
14. Has active Hepatitis B or Hepatitis C virus infection.
15. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
16. Has an active infection requiring systemic therapy.
17. Not applicable: PART 2 ONLY: History of allogeneic tissue/solid organ transplant.
18. Has not adequately recovered from major surgery or has ongoing surgical complications.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

1. Part 1: Percentage of Participants with Dose-limiting toxicities (DLT)
2. Part 1: Percentage of Participants Who Experienced At Least One Adverse Event (AE)
3. Part 1: Percentage of Participants Who Discontinued Study Treatment Due to an AE
4. Not applicable: Part 2: Percentage of Participants with DLT
5. Not applicable: Part 2: Percentage of Participants Who Experienced At Least One AE
6. Not applicable: Part 2: Percentage of Participants Who Discontinued Study Treatment Due to an AE
7. Not applicable: Part 2: Objective Response Rate (ORR)

Secondary endpoints 27

1. Part 1: ORR
2. Not applicable: Part 2: Duration of Response (DOR)
3. Part 1: Maximum Serum Concentration (Cmax) of Sacituzumab Tirumotecan-Antibody-Drug Conjugate (ADC)
4. Part 1: Serum Trough Concentration (Ctrough) of Sacituzumab Tirumotecan-ADC
5. Part 1: Cmax of Free Payload for Sacituzumab Tirumotecan
6. Part 1: Ctrough of Free Payload for Sacituzumab Tirumotecan
7. Part 1: Cmax of Enfortumab Vedotin-ADC
8. Part 1: Ctrough of Enfortumab Vedotin-ADC
9. Part 1: Cmax of Free Payload for Enfortumab Vedotin
10. Part 1: Ctrough of Free Payload for Enfortumab Vedotin
11. Part 1: Incidence of Antidrug Antibodies (ADA) to Sacituzumab Tirumotecan
12. Part 1: Incidence of ADA to Enfortumab Vedotin
13. Not applicable: Part 2: Cmax of Sacituzumab Tirumotecan-ADC
14. Not applicable: Part 2: Ctrough of Sacituzumab Tirumotecan-ADC
15. Not applicable: Part 2: Cmax of Free Payload for Sacituzumab Tirumotecan
16. Not applicable: Part 2: Ctrough of Free Payload for Sacituzumab Tirumotecan
17. Not applicable: Part 2: Cmax of Enfortumab Vedotin-ADC
18. Not applicable: Part 2: Ctrough of Enfortumab Vedotin-ADC
19. Not applicable: Part 2: Cmax of Free Payload for Enfortumab Vedotin
20. Not applicable: Part 2: Ctrough of Free Payload for Enfortumab Vedotin
21. Not applicable: Part 2: Cmax of Pembrolizumab-ADC
22. Not applicable: Part 2: Ctrough of Pembrolizumab-ADC
23. Not applicable: Part 2: Cmax of Free Payload for Pembrolizumab
24. Not applicable: Part 2: Ctrough of Free Payload for Pembrolizumab
25. Not applicable: Part 2: Incidence of ADA to Sacituzumab Tirumotecan
26. Not applicable: Part 2: Incidence of ADA to Enfortumab Vedotin
27. Not applicable: Part 2: Incidence of ADA to Pembrolizumab

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Chethan Ramamurthy

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Chethan Ramamurthy

Third parties 6

Locations

5 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 31 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications